Definition
A.Tuberculosis (TB) is an infectious disease. It is a granulomatous disease caused by Mycobacterium tuberculosis, Mycobacterium bovis, and other mycobacteria. Humans are the only reservoirs for M. tuberculosis. TB may involve multiple organs, including the lungs, liver, spleen, kidney, eyes, brain, spine, and bone.
B.In most immunocompetent individuals, macrophages are successful in containing the bacilli, and the infection is self-limited and often subclinical. As many as 5% of adults with primary TB are asymptomatic with approximately 41% of cases worldwide being undiagnosed. When the pulmonary macrophages are unable to contain the bacilli, it leads to clinically apparent infection-progressive primary TB.
C.Postprimary (reactivation) TB occurs when the initial infection is successfully contained by the pulmonary macrophages, with bacilli remaining viable within the macrophages. Infection results when the host’s immune status (T cells) is compromised.
D.Patients with fever of unknown origin, failure to thrive, significant weight loss, or unexplained lymphadenopathy should be evaluated for TB.
E.The lungs are the most common site for the development of TB; 85% of symptomatic patients present with pulmonary complaints.
Incidence
A.TB is a worldwide infection and is considered a global public health emergency by the World Health Organization (WHO). One-third of the world population is infected:
1.The WHO reports more than nine million new cases of TB every year.
2.TB can affect any age group. Over 60% of the cases are 25 to 40 years old.
3.TB is the leading cause of death for those infected with HIV.
4.The incidence of TB in the United States is 2.9 cases per 100,000 population.
5.Due to the high risk among immigrants, California, New York, Texas, and Florida accounted for half of the TB cases reported in the United States.
B.Postprimary TB is a significant cause of worldwide morbidity and mortality. Pulmonary morbidity results from a chronic cough, hemoptysis, fibrosis, superinfection, bronchial stenosis, repeated pulmonary infections, or empyema. Morbidity also arises from chronic TB osteomyelitis, chronic renal insufficiency, and central nervous system (CNS) TB.
Pathogenesis
A.Mycobacteria are non–spore-forming, slow-growing bacilli. TB infection occurs by means of inhalation of airborne bacillus droplets from an infected host. The development of an infection depends on prolonged exposure (weeks) to an individual with active pulmonary TB. Bacilli travel through the pulmonary lymphatics or enter the vascular system and are disseminated to the brain, meninges, eyes, bones, joints, lymph nodes, kidneys, intestines, larynx, and skin. The incubation period from infection to positive skin test reaction is 2 to 10 weeks, although disease may not occur for many years or may never occur. The risk of disease is greatest within 2 years following infection.
Predisposing Factors
A.Exposure to someone with active disease, including household contact.
B.High-risk groups: Minorities, birth in TB-endemic country, prisoners, nursing home residents, teachers, indigents, migrant workers, and healthcare providers.
C.HIV infection is one of the most significant risk factors for TB.
D.Steroid therapy, cancer chemotherapy, and hematologic malignancies increase the risk of TB.
E.Tumor necrosis factor-alpha (TNF-alpha) antagonists used for rheumatoid arthritis, psoriasis, and other autoimmune disease are associated with a significant risk for TB. Prior to beginning any TNF-alpha treatment, a TB skin test should be administered.
F.Non-TB infections such as measles, varicella, and pertussis may activate quiescent TB.
G.Smoking.
H.Malnutrition.
I.Alcoholism.
J.Intravenous (IV) drug abuse.
K.Congenital TB (rare).
L.Poverty.
Common Complaints
A.Fever (usually low grade at onset but becoming marked with progression of disease).
B.Malaise.
C.Weight loss/difficulty gaining weight.
D.Cough.
E.Night sweats.
F.Chills.
G.Occasional hemoptysis.
H.Fatigue.
I.Anorexia.
Other Signs and Symptoms
A.Pulmonary TB: Fatigue, irritability, undernutrition, with or without fever and cough.
B.Glandular TB: Chronic cervical adenitis.
C.Meningeal TB: Fever and meningeal signs, positive cerebrospinal fluid.
D.Skeletal TB: Back pain or stiffness, lower-extremity paralysis, tuberculous arthritis usually involves only one joint (most often the hip or knee, followed by the ankle, elbow, wrist, and shoulder).
E.Genitourinary TB: Flank pain, dysuria, frequent urination, pen-painful scrotal mass, prostatitis, orchitis, or epididymitis; in women symptoms mimic pelvic inflammatory disease.
F.Gastrointestinal TB: Referable to the infected site including nonhealing ulcers in the mouth or anus, difficulty swallowing (esophageal disease), abdominal pain mimicking peptic ulcer disease, malabsorption, pain, diarrhea, or hematochezia.
Subjective Data
A.Determine onset, duration, and course of illness.
B.Review symptom history: Fever, night sweats, chills, or cough.
C.Review history of weight loss.
D.Review exposure history to someone who has TB and date of last screening.
E.What is the patient’s living situation?
F.Review travel history to endemic areas with TB, including China, Pakistan, the Philippines, Thailand, Indonesia, Bangladesh, and the Democratic Republic of Congo.
G.Review HIV status or need for testing.
Physical Examination
A complete physical examination is mandatory. Physical findings of pulmonary TB are not specific and usually are absent in mild or moderate disease.
A.Record temperature, respirations, pulse, blood pressure (BP)„ and weight. Compare weight to previous readings in past 12 months.
B.Inspect:
1.Observe overall appearance.
2.Check skin for pallor.
3.Inspect eyes, ears, nose, and throat. Evaluate for nonhealing ulcers in the mouth or anus.
C.Auscultate:
1.Auscultate heart.
2.Auscultate lungs and chest for the following:
a.Rales in upper posterior chest.
b.Bronchophony (voice sounds louder than usual).
c.Whispered pectoriloquy: Patient’s whispered sounds are louder than normal.
D.Percuss chest.
E.Palpate:
1.Palpate for lymphadenopathy, usually anterior or posterior cervical and supraclavicular nodes. Less commonly involved lymph nodes include submandibular, axillary, and inguinal lymph nodes.
2.Palpate to evaluate hepatosplenomegaly.
F.Neurologic examination:
1.Evaluate the presence of nuchal rigidity.
2.Assess deep tendon reflexes.
Diagnostic Tests
Diagnosis is based on a combination of purified protein derivative (PPD) skin testing, serum testing with interferongamma release assays (IGRAs), and sputum cultures. Bronchoscopy may be required to obtain specimens. Patients with primary TB may not undergo imaging; however, conventional chest radiograph (CXR) may be performed, and 15% of patients with primary TB have normal CXR findings.
Patients with progressive primary or postprimary TB may need a CT to evaluate parenchymal involvement, satellite lesions, bronchogenic spread, and miliary disease. MRI may be ordered to evaluate complications, such as the extent of thoracic wall involvement with empyema.
A.Tuberculin skin test using the Mantoux test is the recommended method. The dosage of 0.1 mL or 5 tuberculin units (TU) of PPD should be injected intradermally into the volar aspect of the forearm using a 27-gauge needle. A wheel should be raised and should measure approximately 6 to 10 mm in diameter. Skilled personnel should read the test in 48 to 72 hours after administration. Measure the amount of induration and not the erythema. Measure transverse to the long axis of the forearm (see Table 12.3).
1.Sputum culture with acid-fast smear; nasopharyngeal secretions and saliva are not acceptable.
B.The FDA has approved QuantiFERON-TB Gold as an alternative TB test for detecting both TB and latent TB infection.
C.Annual Mantoux tests for those at high risk. There is no need to repeat PPD once the patient has reacted and had a positive PPD. A two-step test is recommended for initial screening only.
D.Anteroposterior (AP) and lateral CXR films: Snowstorm
appearance indicates miliary TB; segmental consolidation and hilar adenopathy are common; pleural effusion may be present.
E.Complete blood count (CBC) with differential.
F.IGRA test.
G.HIV testing as indicated by risk factors to guide management.
H.Pregnancy test (if indicated) to guide management.
Differential Diagnoses
A.TB.
B.Bronchiectasis.
C.Asthma.
D.Histoplasmosis.
E.Coccidioidomycosis.
F.Blastomycosis.
G.Malignancies.
H.Other pulmonary infections.
I.Aspiration pneumonia.
Plan
A.General interventions:
1.Report all suspected and confirmed cases of TB to the local health department.
2.Directly observed therapy (DOT) is mandatory for the treatment of patients with coexistent HIV disease, those with multidrug-resistant (MDR) TB, and those who may be noncompliant.
3.Educate patients regarding compliance to therapy, adverse effect of medications, and follow-up care.
B.Pharmaceutical therapy: The American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC) provide the standard guidelines for therapy:
1.Refer to the CDC for up-to-date guidelines on treatment: www.cdc.gov/tb/publications/guidelines/treatment.htm. Medication protocols vary and include the following first-line agents: isoniazid (INH), rifampin (Rifadin), pyrazinamide (Tebrazid), and ethambutol (Etibi):
a.INH (Laniazid, Nydrazid) dosing:
i.Adults: 5 to 10 mg/kg by mouth (not to exceed 300 mg/d).
TABLE 12.3 Interpretation of Mantoux Tuberculin Skin Test
| Positive Reaction—Induration Size | Risk Factors |
| 5 mm or more | Close contact with known or suspected TB; immunosuppressive conditions (e.g., HIV); on immunosuppressive medications; or an abnormal chest x-ray—consistent with active TB, previously active TB, or clinical evidence of the disease. |
| 10 mm or more | High-risk categories (i.e., homeless, HIV infected, users of illicit drugs, residents in nursing homes, incarcerated, or institutionalized); travel histories to high-prevalence areas of world. |
| 15 mm or more | Any age without any risk factors for TB. |
TB, tuberculosis.
b.Rifampin (Rifadin) dosing:
i.Adults: 600 mg by mouth every day.
c.Pyrazinamide (Tebrazid) dosing:
i.Adults: 15 to 30 mg/kg by mouth every day; not to exceed 2 g/d.
d.Ethambutol (Myambutol) dosing:
i.Adults with no previous anti-TB therapy: 15 mg/kg by mouth every day.
ii.Adults with previous therapy: 25 mg/kg by mouth every day.
2.Compliance with drug regimen is most important.
3.Drug resistance averages 5% to 10% nationally and is increasing.
4.The bacilli Calmette-Guerin (BCG) vaccine is available in TB-endemic countries for the prevention of childhood TB-related meningitis and miliary TB. BCG is a live vaccine. BCG does not prevent infection with M. tuberculosis.
Follow-Up
A.Regular follow-up every 4 to 8 weeks to ensure compliance and to monitor the adverse effects and response of the medications.
B.Repeat CXR may be performed after 2 to 3 months of therapy to observe the response to treatment for patients with pulmonary TB.
C.Consider monitoring liver enzymes monthly in the following patients:
1.Severe or disseminated TB.
2.Concurrent or recent hepatic disease or hepatobiliary tract disease from other causes.
3.Those receiving high doses of INH (10 mg/kg/d) in combination with rifampin, pyrazinamide, or both drugs.